DESCRIPTION (Adapted from the application): Phosphoinositide (PI) polyphosphates (PIPns) are key signaling molecules in cellular communication. In particular, isozymes of PI 3-kinase, PI 4-kinase and PI 5-kinase have been identified and are important in insulin signaling, apoptosis, cytoskeletal remodeling and protein trafficking. Few specific inhibitors for these enzymes exist. The development of targeted therapeutic agents would be substantially enhanced with rapid assays for lipid kinase activities that could be employed in a 96-well format. Vast libraries of potential inhibitors could be screened with such a high throughput assay. The applicant has developed syntheses of PIPns, including functionalized "tetherable" acyl chains. In the second tier strategy, both the long-chain and functionalized PIPns will be employed to prepare assay plates containing a specific immobilized PIPn using a proprietary strategy. The applicant proposes to focus on the use of PI, PI(4)P, PI(5)P, and PI(4,5)P2 as substrates for PI 3-kinase to develop and optimize an assay kit and test benchmark inhibitors of this enzyme. Subsequent development of reagent kits for other kinases and the screening of potential inhibitors will be pursued following this feasibility study. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE